Cyclin A2 modulates EMT via β-catenin and phospholipase C pathways
| Autor: | Abdallah Hamieh, Bénédicte Lemmers, Conception Paul, Youssef Anouar, Michael Hahne, Jean-Marie Blanchard, Caroline Cheung, Nawal Bendris |
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| Přispěvatelé: | Unité différenciation épidermique et auto-immunité rhumatoïde (UDEAR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Laboratoire d'Automatique, de Mécanique et d'Informatique industrielles et Humaines - UMR 8201 (LAMIH), Université de Valenciennes et du Hainaut-Cambrésis (UVHC)-Centre National de la Recherche Scientifique (CNRS), Différenciation et communication neuronale et neuroendocrine (DC2N), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM) |
| Rok vydání: | 2014 |
| Předmět: |
Cancer Research
Frizzled Epithelial-Mesenchymal Transition MAP Kinase Signaling System [SDV.CAN]Life Sciences [q-bio]/Cancer [SDV.BC]Life Sciences [q-bio]/Cellular Biology 03 medical and health sciences 0302 clinical medicine Mammary Glands Animal Animal/metabolism/pathology Type C Phospholipases/genetics/*metabolism Wnt Signaling Pathway/drug effects beta Catenin/*metabolism Downregulation and upregulation Phosphoinositide phospholipase C Animals Humans [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology Wnt Signaling Pathway beta Catenin 030304 developmental biology Cyclin 0303 health sciences Phospholipase C Chemistry [SDV.BA]Life Sciences [q-bio]/Animal biology Wnt signaling pathway General Medicine Cyclic AMP-Dependent Protein Kinases Cell biology HEK293 Cells 030220 oncology & carcinogenesis Catenin Type C Phospholipases [SDV.IMM]Life Sciences [q-bio]/Immunology Female Animals Cyclic AMP-Dependent Protein Kinases/metabolism Cyclin A2/genetics/*metabolism Epithelial-Mesenchymal Transition/drug effects/*physiology Female HEK293 Cells Humans MAP Kinase Signaling System/drug effects Mammary Glands Cyclin A2 |
| Zdroj: | Carcinogenesis Carcinogenesis, Oxford University Press (OUP), 2015, 36 (8), pp.914--24. ⟨10.1093/carcin/bgv069⟩ Carcinogenesis, Oxford University Press (OUP), 2015, 36 (8), pp.914-924. ⟨10.1093/carcin/bgv069⟩ |
| ISSN: | 1460-2180 0143-3334 |
| Popis: | International audience; We have previously demonstrated that Cyclin A2 is involved in cytoskeletal dynamics, epithelial-mesenchymal transition (EMT) and metastasis. This phenotype was potentiated by activated oncogenic H-Ras. However, the mechanisms governing EMT in these cells have not yet been elucidated. Here, we dissected the pathways that are responsible for EMT in cells deficient for Cyclin A2. In Cyclin A2-depleted normal murine mammary gland (NMuMG) cells expressing RasV12, we found that β-catenin was liberated from the cell membrane and cell-cell junctions and underwent nuclear translocation and activation. Components of the canonical wingless (WNT) pathway, including WNT8b, WNT10a, WNT10b, frizzled 1 and 2 and TCF4 were upregulated at the messenger RNA and protein levels following Cyclin A2 depletion. However, suppression of the WNT pathway using the acetyltransferase porcupine inhibitor C59 did not reverse EMT whereas a dominant negative form of TCF4 as well as inhibition of phospholipase C using U73122 were able to do so. This suggests that a WNT-independent mechanism of β-catenin activation via phospholipase C is involved in the EMT induced by Cyclin A2 depletion. Our findings will broaden our knowledge on how Cyclin A2 contributes to EMT and metastasis. |
| Databáze: | OpenAIRE |
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